Brachyury promotes proliferation and migration of colorectal cancer cells by targeting MMP14.

IF 5.3 2区医学 Q1 ONCOLOGY

Cancer Cell International Pub Date : 2025-04-07 DOI:10.1186/s12935-025-03726-w

Ming Chen, Huiheng Qu, Xiao Liang, Ying Huang, Zhengjie Yang, Pei Lu, Keqin Shi, Peng Chen, Yanjing Zhang, Hui Zhou, Jiazeng Xia, Jun Shen

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引用次数: 0

Abstract

Background: The incidence and mortality rates of colorectal cancer (CRC) are rising, and it is the second most common cause of cancer-related deaths worldwide. Although the transcription factor, Brachyury is intricately linked with various clinical malignancies, the mechanisms by which it influences CRC cell proliferation and migration are inadequately understood.

Methods: Tissue microarray was used to evaluate Brachyury expression in CRC and adjacent normal tissues. The effects of Brachyury on HCT116 and SW480 CRC cells were also examined in vitro, including using Cell Counting Kit-8, colony formation, and transwell assays, and in vivo through subcutaneous tumorigenesis assays in a nude mouse xenograft model. Chromatin immunoprecipitation was used to evaluate Brachyury binding to the MMP14 promoter and its impact on MMP14 expression. Rescue experiments were used to elucidate MMP14's role in mediating Brachyury's effect on CRC cell behavior.

Results: Brachyury expression was significantly higher in CRC tissues than in adjacent normal tissues, and it promotes CRC oncogenesis in vitro and in vivo. Rescue experiments established MMP14 as a direct, downstream Brachyury target, affirming that MMP14 enhanced Brachyury-driven CRC cell proliferation.

Conclusion: Our findings highlight targeting the Brachyury-MMP14 axis as a potential novel approach for CRC clinical therapy.

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Brachyury通过靶向MMP14促进结直肠癌细胞的增殖和迁移。

背景：结直肠癌（CRC）的发病率和死亡率正在上升，是全球癌症相关死亡的第二大常见原因。尽管Brachyury转录因子与多种临床恶性肿瘤有着复杂的联系，但其影响结直肠癌细胞增殖和迁移的机制尚不清楚。方法：采用组织芯片技术检测Brachyury在结直肠癌及邻近正常组织中的表达。Brachyury对HCT116和SW480结直肠癌细胞的影响也在体外进行了检测，包括使用细胞计数试剂盒-8、集落形成和transwell试验，以及在体内通过裸鼠异种移植模型的皮下肿瘤发生试验。采用染色质免疫沉淀法评估Brachyury与MMP14启动子的结合及其对MMP14表达的影响。我们利用挽救实验来阐明MMP14介导Brachyury对结直肠癌细胞行为的影响。结果：Brachyury在结直肠癌组织中的表达明显高于邻近正常组织，在体外和体内均促进结直肠癌的发生。挽救实验证实MMP14是Brachyury的直接下游靶点，证实了MMP14增强Brachyury驱动的CRC细胞增殖。结论：我们的研究结果强调靶向Brachyury-MMP14轴是CRC临床治疗的潜在新方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.